Initiation of TCR Phosphorylation and Signal Transduction

Recent data with CD8+ T cells show that the initial phase of T cell receptor (TCR) binding to MHC–peptide (MHCp) is quickly followed by a second, stronger, binding phase representing the binding of CD8 to the MHCp. This second phase requires signaling by a Src-family kinase such as Lck. These data point out two aspects of the initial stage of TCR signaling that have not yet been clearly resolved. Firstly, how and by which Src-family kinase, is the initial phosphorylation of CD3ζ accomplished, given that the Lck associated with the co-receptors (CD4 or CD8) is not yet available. Secondly, what is the mechanism by which the co-receptor is brought close to the bound TCR before the co-receptor binds to MHCp

Poziom poczucia koherencji u narciarzy niepełnosprawnych i pełnosprawnych w Polsce i w USA

In the last few years, adaptive sport and adaptive physical education as forms of physiotherapy have gained increasing interest around the world and also in Poland. This thesis discusses application of alpine skiing in social rehabilitation for the persons with disabilities.It describes how skiing can help overcoming problems with personal and social behavior and influence on looking at once life, in order to compare the sense of coherence of skiers with and without disabilities.The research involved 31 Polish (16 disabled and 15 without disabilities) and 27 American (12 disabled and 15 without disabilities) responders. It was based on a Sense of Coherence Questionnaire SOC-13 by Aaron Antonovsky.Conclusions: The level of coherence among disabled skiers is comparable to those without disabilities

Coaching in the professional and personal development of nurses

Wprowadzenie . Deficyt pielęgniarek obserwowany w UE (Unii Europejskiej) może mieć różne przyczyny m. in.: mało atrakcyjne warunki pracy, niepodejmowanie pracy w tej profesji (pomimo posiadanego wykształcenia) oraz wysoki wskaźnik wypalenia zawodowego. Wyzwaniem dla pracodawców oraz instytucji zajmujących się problemami współczesnego pielęgniarstwa pozostaje problem zachęcenia adeptów kierunku do podjęcia pracy w zawodzie i pozostania w nim na dłużej. Także duże znaczenie ma nauczenie pielęgniarek jak chronić się przed wypaleniem zawodowym, łączyć ambicje zawodowe z potrzebami rodziny a przede wszystkim osobistą satysfakcją z życia. Pośród potencjalnych rozwiązań wspomagających świadome zaplanowanie życia osobistego i dalszego rozwoju zawodowego, warto rozważyć wsparcie coacha, podobnie jak to ma miejsce w innych zawodach. Cel. Analiza sytuacji zawodowej pielęgniarek w kontekście potrzeby indywidualnego rozwoju z zastosowaniem metody coachingu. Metodyka. Zastosowano metodę analizy i krytyki piśmiennictwa naukowego. Podsumowanie i wnioski. Wykorzystanie elementów coachingu stwarza szansę, by pielęgniarka/pielęgniarz w sposób świadomy i planowy projektowali przebieg swojego rozwoju zawodowego synchronicznie z potrzebami i oczekiwaniami w życiu osobistym, rodzinnym i społecznym. Dodatkowymi korzyściami z zastosowania tej formy wsparcia są umiejętność lepszego radzenia sobie ze stresem, zachowanie równowagi pomiędzy pracą a życiem osobistym (tzw. work-life balance) oraz prewencja wypalenia zawodowego.Introduction . Shortage of nurses reported in the EU (European Union) among other causes is related to: non-attractive work conditions, lack of willingness to take up job as a nurse (despite their education), and high risk of professional burnout. Encouraging graduates to take up a job in the profession and remain is a challenge for employers and institutions involved in the problems of modern nursing. Teaching nurses how to: protect themselves from professional burnout, how to combine career ambitions, family needs and above all personal satisfaction is of utmost importance. Amongst possible solutions which enhance planning of career and personal development in a deliberate manner, as is the case in other professions, it may be worth considering the support of a coach. Aim. Analysis of the professional situation of nurses in the context of need for individual development using the coaching method. Method. A method of analysis and criticism of the literature was used. Conclusions and results. Coaching gives an op po rtun ity for conscious planning process of nurse professional development in synchrony with needs and expectations for personal, family and social life. Better stress management, maintaining work-life balance and professional burnout prevention are benefits provided by this approach

Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression : a meta-analysis of randomized clinical trials

Background Due to unmet clinical needs for efficient drugs with a rapid onset of antidepressant effects, we aimed to evaluate the efficacy of single-dose ketamine in different subgroups of patients with major depression and establish whether repeated ketamine administration could be a viable strategy to maintain treatment gains. Methods Electronic databases (Medline via PubMed, Embase, Cochrane Library, Trip Database) were systematically searched until February 22, 2019, for published peer-reviewed randomized controlled trials (RCTs) concerning a single and repeated administration of ketamine in patients with major depression. All relevant RCTs were selected and critically appraised, and a meta-analysis of eligible studies was performed. Results A total of 20 studies were included in the meta-analysis. The largest effect of ketamine vs. controls in reducing depressive symptoms was observed at 24 h (SMD = - 0.89; 95% CI - 1.24; - 0.53; p < 0.00001); however, a significant difference was shown for up to 7 days after a single dose. Significant differences compared with controls were observed for up to 7 days in treatment-resistant patients and when ketamine was added to ongoing antidepressant treatment, while there were no significant differences at 7 days when ketamine was used as monotherapy. In patients with major depression, initial antidepressant effects of ketamine were maintained during repeated dosing. At 2-3 weeks of repeated ketamine treatment, significant reduction of depression severity scores was observed: SMD = - 0.70; 95% CI - 1.15; - 0.25 or SMD = - 0.81; 95% CI - 1.41; - 0.20 (depending on the dosing regimen used); p ≤ 0.009 vs placebo. Conclusions Our meta-analysis revealed rapid and robust antidepressant effects of single-dose ketamine in patients with treatment-resistant depression (TRD). By pooling data from RCTs, we showed for the first time that repeated ketamine administration is effective in sustaining initial antidepressant effects observed after single dosing

Quality of life of patients type A hemophilia

Bibliogr. s. 122Hemophilia is a genetic disease characterized by blood clotting abnormalities. It most commonly affects males. Hemophilia not only results in musculoskeletal system damage due to repeated joint bleeds, but also provokes various emotional reactions in patients. It affects health related quality of life. Quality of life assessment in hemophilia A patients. The study included 40 males with hemophilia A, members of the Polish Hemophilia Society - Division in Cracow. An original questionnaire and World Health Organization Quality of Life scale were used. Quality of life of the study population was moderate. The most important factors influencing quality of life were occupational activity and home treatment with factor concentrate

Ectomycorrhizal Plant-Fungal Co-invasions as Natural Experiments for Connecting Plant and Fungal Traits to Their Ecosystem Consequences

Introductions and invasions by fungi, especially pathogens and mycorrhizal fungi, are widespread and potentially highly consequential for native ecosystems, but may also offer opportunities for linking microbial traits to their ecosystem functions. In particular, treating ectomycorrhizal (EM) invasions, i.e., co-invasions by EM fungi and their EM host plants, as natural experiments may offer a powerful approach for testing how microbial traits influence ecosystem functions. Forests dominated by EM symbiosis have unique biogeochemistry whereby the secretions of EM plants and fungi affect carbon (C) and nutrient cycling; moreover, particular lineages of EM fungi have unique functional traits. EM invasions may therefore alter the biogeochemistry of the native ecosystems they invade, especially nitrogen (N) and C cycling. By identifying “response traits” that favor the success of fungi in introductions and invasions (e.g., spore dispersal and germination) and their correlations with “effect traits” (e.g., nutrient-cycling enzymes) that can alter N and C cycling (and affect other coupled elemental cycles), one may be able to predict the functional consequences for ecosystems of fungal invasions using biogeochemistry models that incorporate fungal traits. Here, we review what is already known about how EM fungal community composition, traits, and ecosystem functions differ between native and exotic populations, focusing on the example of EM fungi associated with species of Pinus introduced from the Northern into the Southern Hemisphere. We develop hypotheses on how effects of introduced and invasive EM fungi may depend on interactions between soil N availability in the exotic range and EM fungal traits. We discuss how such hypotheses could be tested by utilizing Pinus introductions and invasions as a model system, especially when combined with controlled laboratory experiments. Finally, we illustrate how ecosystem modeling can be used to link fungal traits to their consequences for ecosystem N and C cycling in the context of biological invasions, and we highlight exciting avenues for future directions in understanding EM invasion.Fil: Hoeksema, Jason D.. University of Mississippi; Estados UnidosFil: Averill, Colin. No especifíca;Fil: Bhatnagar, Jennifer M.. Boston University; Estados UnidosFil: Brzostek, Edward. West Virginia University; Estados UnidosFil: Buscardo, Erika. Universidade do Brasília; BrasilFil: Chen, Ko Hsuan. University of Florida; Estados UnidosFil: Liao, Hui Ling. University of Florida; Estados UnidosFil: Nagy, Laszlo. Universidade Estadual de Campinas; BrasilFil: Policelli, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Ridgeway, Joanna. West Virginia University; Estados UnidosFil: Rojas, J. Alejandro. University of Arkansas for Medical Sciences; Estados UnidosFil: Vilgalys, Rytas. University of Duke; Estados Unido

Ligand-engaged TCR is triggered by Lck not associated with CD8 coreceptor

Producción CientíficaThe earliest molecular events in T-cell recognition have not yet been fully described, and the initial T-cell receptor (TCR)-triggering mechanism remains a subject of controversy. Here, using total internal reflection/Forster resonance energy transfer microscopy, we observe a two-stage interaction between TCR, CD8 and major histocompatibility complex (MHC)-peptide. There is an early (within seconds) interaction between CD3ζ and the coreceptor CD8 that is independent of the binding of CD8 to MHC, but that requires CD8 association with Lck. Later (several minutes) CD3ζ–CD8 interactions require CD8–MHC binding. Lck can be found free or bound to the coreceptor. This work indicates that the initial TCR-triggering event is induced by free Lck. The early signalling events that trigger initial T-cell receptor signalling are not clearly defined. Here the authors show that this occurs in two stages, the first between the CD8 coreceptor and CD3 requiring Lck association to CD8, while the second interaction requires binding of major histocompatibility molecules

Coreceptor affinity for MHC defines peptide specificity requirements for TCR interaction with coagonist peptide-MHC

Recent work has demonstrated that nonstimulatory endogenous peptides can enhance T cell recognition of antigen, but MHCI- and MHCII-restricted systems have generated very different results. MHCII-restricted TCRs need to interact with the nonstimulatory peptide–MHC (pMHC), showing peptide specificity for activation enhancers or coagonists. In contrast, the MHCI-restricted cells studied to date show no such peptide specificity for coagonists, suggesting that CD8 binding to noncognate MHCI is more important. Here we show how this dichotomy can be resolved by varying CD8 and TCR binding to agonist and coagonists coupled with computer simulations, and we identify two distinct mechanisms by which CD8 influences the peptide specificity of coagonism. Mechanism 1 identifies the requirement of CD8 binding to noncognate ligand and suggests a direct relationship between the magnitude of coagonism and CD8 affinity for coagonist pMHCI. Mechanism 2 describes how the affinity of CD8 for agonist pMHCI changes the requirement for specific coagonist peptides. MHCs that bind CD8 strongly were tolerant of all or most peptides as coagonists, but weaker CD8-binding MHCs required stronger TCR binding to coagonist, limiting the potential coagonist peptides. These findings in MHCI systems also explain peptide-specific coagonism in MHCII-restricted cells, as CD4–MHCII interaction is generally weaker than CD8–MHCI.National Institutes of Health (U.S.). Pioneer Awar